The long-term goal of this project is the development of radiopharmaceuticals for diagnosis of Dementia with Lewy Bodies (DLB). DLB is the second most common cause of dementia in the United States; although the disease requires specific pharmacologic management, current diagnostic methods are extremely inaccurate. DLB is often misdiagnosed as Alzheimer's disease or Parkinson's disease with dementia. This project is driven by the hypothesis that in vivo detection of synuclein pathology by positron emission computed tomography imaging (using radiolabeled synuclein binding probes) would allow for the early and definitive diagnosis of DLB, thus improving treatment of these patients. Phase I of this project will assess the feasibility of this approach through the synthesis and in vitro evaluation of potential synuclein probes. Specific aims of Phase I include: 1) Synthesis of proposed probes; 2) Testing the probes ability to label brain synuclein pathology; and 3) Measuring the affinity of the probes for synuclein pathology. If suitable probes are identified, Phase II will optimize the structure and test biodistribution and efficacy of the probes in transgenic mice. Probes with appropriate properties will be selected for clinical development to yield an innovative product for the evaluation and diagnosis of DLB.